Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Aug;61(8):1142-1149.
doi: 10.1194/jlr.S120000720. Epub 2020 Jun 1.

Lecithin:cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings

Kaare R Norum  1 , Alan T Remaley  2 , Helena E Miettinen  3 , Erik H Strøm  4 , Bruno E P Balbo  5 , Carlos A T L Sampaio  5 , Ingrid Wiig  6 , Jan Albert Kuivenhoven  7 , Laura Calabresi  8 , John J Tesmer  9 , Mingyue Zhou  10 , Dominic S Ng  11 , Bjørn Skeie  12 , Sotirios K Karathanasis  2   13 , Kelly A Manthei  14 , Kjetil Retterstøl  15   16
Affiliations

Lecithin:cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings

Kaare R Norum et al. J Lipid Res. 2020 Aug.

Abstract

LCAT converts free cholesterol to cholesteryl esters in the process of reverse cholesterol transport. Familial LCAT deficiency (FLD) is a genetic disease that was first described by Kaare R. Norum and Egil Gjone in 1967. This report is a summary from a 2017 symposium where Dr. Norum recounted the history of FLD and leading experts on LCAT shared their results. The Tesmer laboratory shared structural findings on LCAT and the close homolog, lysosomal phospholipase A2. Results from studies of FLD patients in Finland, Brazil, Norway, and Italy were presented, as well as the status of a patient registry. Drs. Kuivenhoven and Calabresi presented data from carriers of genetic mutations suggesting that FLD does not necessarily accelerate atherosclerosis. Dr. Ng shared that LCAT-null mice were protected from diet-induced obesity, insulin resistance, and nonalcoholic fatty liver disease. Dr. Zhou presented multiple innovations for increasing LCAT activity for therapeutic purposes, whereas Dr. Remaley showed results from treatment of an FLD patient with recombinant human LCAT (rhLCAT). Dr. Karathanasis showed that rhLCAT infusion in mice stimulates cholesterol efflux and suggested that it could also enhance cholesterol efflux from macrophages. While the role of LCAT in atherosclerosis remains elusive, the consensus is that a continued study of both the enzyme and disease will lead toward better treatments for patients with heart disease and FLD.

Keywords: HDL cholesterol; cardiovascular heart disease; lipoprotein; lipoprotein X.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflicts of interest with the contents of this article.

Figures

Fig. 1.
Fig. 1.
Kaare R. Norum. Photo taken in 2016 by K. Retterstøl.
Fig. 2.
Fig. 2.
Reverse cholesterol transport. Cholesterol is effluxed from arterial macrophages to preβ-HDL, where it is esterified by LCAT. The cholesteryl ester (CE) then enters the center of the HDL and promotes maturation to larger and more spherical particles. HDL transports CEs directly to the liver, or via LDL when they are transferred by CETP. Cholesterol is then excreted in bile and other components are recycled.
Fig. 3.
Fig. 3.
Crystal structures reveal a dynamic lid that shields the active site of LCAT. Two crystal structures are overlaid to highlight lid movement. The closed conformation (Protein Data Bank code 5TXF) is indicated with a filled arrowhead and red lid, and an open state of LCAT (Protein Data Bank code 6MVD) bound to an activator (purple) is indicated with an open arrowhead and magenta lid. Unmodeled residues in the lid are indicated by a dashed line. The α/β-hydrolase domain is colored in orange, the cap domain in blue, and the membrane binding domain in teal. The active site residue Ser181 is indicated with orange ball-and-sticks, whereas Arg244, which is mutated in FLD, is shown in the lid with red and magenta ball-and-sticks. N and C indicate the amino and carboxyl termini, respectively, observed in the structures.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Glomset J. A., Parker F., Tjaden M., and Williams R. H.. 1962. The esterification in vitro of free cholesterol in human and rat plasma. Biochim. Biophys. Acta. 58: 398–406. - PubMed
    1. Glomset J. A. 1962. The mechanism of the plasma cholesterol esterification reaction: plasma fatty acid transferase. Biochim. Biophys. Acta. 65: 128–135. - PubMed
    1. Norum K. R., and Gjone E.. 1967. Familial serum-cholesterol esterification failure. A new inborn error of metabolism. Biochim. Biophys. Acta. 144: 698–700. - PubMed
    1. Ossoli A., Neufeld E. B., Thacker S. G., Vaisman B., Pryor M., Freeman L. A., C. A. Brantner, I. Baranova, N. O. Francone, S. J. Demosky, Jr., et al. . 2016. Lipoprotein X causes renal disease in LCAT deficiency. PLoS One. 11: e0150083. - PMC - PubMed
    1. Holleboom A. G., Jakulj L., Franssen R., Decaris J., Vergeer M., Koetsveld J., J. Luchoomun, A. Glass, M. K. Hellerstein, J. J. P. Kastelein, et al. . 2013. In vivo tissue cholesterol efflux is reduced in carriers of a mutation in APOA1. J. Lipid Res. 54: 1964–1971. - PMC - PubMed

Publication types

Substances

LinkOut - more resources